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Dietary Phosphorus Regulates Serum Fibroblast Growth Factor-23 Concentrations in Healthy Men

Division of Endocrinology (D.M.A.), Department of Medicine, and Division of Pediatric Nephrology (A.A.P.), Department of Pediatrics, University of California, San Francisco, California 94143-0748; and Pharmaceutical Research Laboratory (T.Y.), Kirin Brewery Co. Ltd., Takasaki 370-1295, Japan

Address all correspondence and requests for reprints to: Anthony A. Portale, M.D., 533 Parnassus Avenue, Room U-585, University of California, San Francisco, California 94143-0748. E-mail: aportale{at}peds.ucsf.edu.

Context: Fibroblast growth factor 23 (FGF-23) is important in the regulation of phosphorus and vitamin D metabolism. States of excess circulating FGF-23 are associated with renal phosphate wasting and inappropriately low serum 1,25-dihydroxyvitamin D [1,25(OH)₂D] concentrations. Conversely, states of absent or biologically inactive circulating FGF-23 are associated with increased serum phosphorus and 1,25(OH)₂D concentrations. Restriction of the dietary intake of phosphorus increases renal phosphate reabsorption and 1,25(OH)₂D production, whereas the opposite occurs when dietary phosphorus is supplemented.

Objective: We sought to determine whether serum FGF-23 concentration is regulated by dietary phosphorus and thereby mediates the physiological response of serum 1,25(OH)₂D to changes in dietary phosphorus.

Design, Setting, and Participants: We studied 13 healthy men as inpatients during a 4-wk dietary phosphorus intervention study.

Intervention: Subjects consumed a constant diet that provided 500 mg of phosphorus per day, which was supplemented to achieve three phosphorus intakes, each of 9 d: 1) control = 1500 mg/d; 2) supplemented = 2300 mg/d; 3) restricted = 625 mg/d. Intakes of calcium, sodium, potassium, magnesium, and energy were constant.

Main Outcome Measure: Serum FGF-23, 1,25(OH)₂D, phosphorus, and calcium concentrations were measured.

Results: Serum FGF-23 concentrations decreased significantly from 30.7 ± 8.7 pg/ml during phosphorus supplementation to 19.6 ± 7.0 pg/ml during phosphorus restriction. Serum 1,25(OH)₂D concentrations increased significantly from 29 ± 10 pg/ml (75 ± 26 pmol/liter) during phosphorus supplementation to 40 ± 16 pg/ml (104 ± 42 pmol/liter) during phosphorus restriction (P < 0.001). Serum 1,25(OH)₂D concentrations varied inversely with those of serum FGF-23 (r = –0.67, P < 0.001).

Conclusions: We conclude that in healthy men, changes in dietary phosphorus within the physiological range of intakes regulate serum FGF-23 concentrations and suggest that dietary phosphorus regulation of 1,25(OH)₂D production is mediated, at least in part, by changes in circulating FGF-23.

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